The skull has long served as a barrier to producing ultrasound brain images, causing distortion and attenuation that have limited ultrasound's diagnostic role primarily to detecting blood flow by transcranial Doppler applied to a thin region of the bone. Over the past decade, we have been developing basic techniques to overcome these limits by maximizing energy transfer and minimizing distortion through the bone. This work has culminated in a new technique that holds the potential for producing clear and accurate images in the clinic. Implemented through a custom device, the technique will correct for skull distortion using feedback from an ultrasound applicator that encircles the skull. Optimized beams will be used to produce ultrasound computed tomography (UCT) images, which will display full cross-sections of both the skull and brain, providing user orientation similar to that of CT or MRI. We will use a novel reconstruction method, which has theoretical parallels with radio-frequency-based diffraction tomography, but which further utilizes ultrasound's superior ability to customize the imaging beamshape. Unlike traditional ultrasound, which relies on short pulses for resolution, the method will use one or more single ultrasound frequencies to create an image, permitting a multi-cycle (and subsequently much stronger) imaging signal. The overall goal of the work is produce a portable, non-ionizing diagnostic tool for brain injury and disorders that could be used in remote locations, patient bedside, or for patients whose condition precludes the use of MRI or CT. We plan to develop this technique into a device ready for clinical testing by the end of the grant period. MRI will be used as a benchmark to evaluate the device's success, with quantitative goals aiming at the detection and tracking of millimeter-resolution anatomical features and abnormalities. The project could provide extensive benefits toward early diagnosis of brain disorders and injury as well as offer a new tool for repeated monitoring of known existing conditions. PUBLIC HEALTH RELEVANCE: The skull has severely limited ultrasound's use in the brain. However, we have been developing techniques to overcome these limits, which we will now combine to produce brain images presently only possible using large and high-cost devices, such as MRI and CT. By the end of the proposed project we plan to have a completed and tested device, ready for testing in the clinic.